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ABSTRACT: AIMS: We evaluated pathological features of the ductal carcinoma in situ component of 241 triple negative invasive breast cancers. RESULTS: We found that 151 (62.6%) in situ lesions were of high nuclear grade, and 236 (97.9%) were triple negative (oestrogen receptor, progesterone receptor, cerbB2 negative). Immunohistochemistry for cytokeratin (CK)5/6, CK14, CK17, epidermal growth factor receptor (EGFR), CD117, 34βE12, p63 and smooth muscle actin (SMA) revealed positive staining in 5 (2.1%), 60 (24.9%), 69 (28.6%), 37 (15.4%), 69 (28.6%), 137 (56.8%), 3 (1.2%) and 22 (9.1%) in situ ductal components respectively, with fair to substantial agreement of staining results (positive versus negative) between in situ and corresponding invasive elements for CK5/6, CK14, CK17, EGFR, CD117 and 34βE12; but none to fair agreement for p63 and SMA respectively. When the tri-panel of CK14, EGFR and 34βE12 was used to define the basal phenotype, 68% revealed basal-like expression of both in situ and invasive components of the same case. CONCLUSIONS: Our data support the notion that triple negative ductal carcinoma in situ is the precursor of the corresponding invasive counterpart, and that basal-like expression is maintained in the majority of invasive cancers associated with basal-like in situ disease. Future studies that prospectively evaluate morphological and biological characteristics of invasive cancers that develop from triple negative and basal-like ductal carcinoma in situ lesions will assist in validating these findings.
Journal of clinical pathology 03/2013; · 2.43 Impact Factor
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Sameer Phalke,
Slim Mzoughi,
Marco Bezzi,
Nancy Jennifer,
Wei Chuen Mok,
Diana H P Low, Aye Aye Thike,
Vladimir A Kuznetsov,
Puay Hoon Tan,
P Mathijs Voorhoeve,
Ernesto Guccione
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ABSTRACT: p21 is a potent cyclin-dependent kinase inhibitor that plays a role in promoting G1 cell cycle arrest and cellular senescence. Consistent with this role, p21 is a downstream target of several tumour suppressors and oncogenes, and it is downregulated in the majority of tumours, including breast cancer. Here, we report that protein arginine methyltransferase 6 (PRMT6), a type I PRMT known to act as a transcriptional cofactor, directly represses the p21 promoter. PRMT6 knock-down (KD) results in a p21 derepression in breast cancer cells, which is p53-independent, and leads to cell cycle arrest, cellular senescence and reduced growth in soft agar assays and in severe combined immunodeficiency (SCID) mice for all the cancer lines examined. We finally show that bypassing the p21-mediated arrest rescues PRMT6 KD cells from senescence, and it restores their ability to grow on soft agar. We conclude that PRMT6 acts as an oncogene in breast cancer cells, promoting growth and preventing senescence, making it an attractive target for cancer therapy.
Nucleic Acids Research 09/2012; 40(19):9534-9542. · 8.03 Impact Factor
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ABSTRACT: Iqbal J, Thike A A, Cheok P Y, Tse G M-K & Tan P H (2012) Histopathology Insulin growth factor receptor-1 expression and loss of PTEN protein predict early recurrence in triple-negative breast cancer Aims: Insulin-like growth factor receptor-1 (IGFR-1) and its signalling axis promote tumorigenesis, metastasis, and resistance to existing forms of cancer therapy, and have become a major focus for the development of anticancer drugs. As oncological management options for triple-negative breast cancers (TNBCs) are limited, there is potential for the rapid development of novel selective anticancer agents specifically targeting components of the PTEN-phosphoinositide 3-kinase-AKT pathway, including the phosphorylated form of AKT (pAKT) and the tumour suppressor molecule PTEN. The aim of this study was to conduct immunohistochemical analyses to examine the levels of PTEN, IGFR-1 and pAKT expression in TNBCs, and determine whether these levels correlated with poor prognosis in this subset of aggressive breast cancers. Methods and results: Immunohistochemistry was performed on paraffin-embedded tumour tissues from a consecutive cohort of 144 female patients diagnosed with TNBC. Associations of IGFR-1, PTEN and pAKT expression with clinicopathological parameters, disease-free survival (DFS) and overall survival (OS) were evaluated. There were significant increases in IGFR-1 expression (99%) and pAKT expression (92%) with concomitant loss of PTEN expression in the majority of cases (63%). Increased IGFR-1 expression and loss of PTEN expression were associated with reduced OS and DFS, respectively. pAKT expression showed a strong correlation with basal-like expression. Combinatorial immunophenotypic analyses showed that loss of PTEN expression with concomitant IGFR-1 expression correlated with poor DFS. Conclusions: A high percentage of PTEN loss with overexpression of IGFR-1 and pAKT in TNBC indicates the potential of these molecules for predicting early recurrence and/or as targets in the formulation of effective alternative therapy regimens.
Histopathology 07/2012; · 3.08 Impact Factor
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ABSTRACT: To determine the frequency, pattern and distribution of stromal keratin expression in phyllodes tumours if any, which may impact diagnostic approaches.
The clinicopathological features of 109 phyllodes tumours comprising 70 (64.2%) benign, 30 (27.5%) borderline and nine (8.3%) malignant grades were evaluated, and the immunohistochemical expression of a keratin panel (MNF116, 34βE12, CK7, CK14, AE1/3, Cam5.2), p63 and CD34 in their stromal component was assessed.
There was focal and patchy cytoplasmic keratin staining in 1-5% of stromal cells in 13 (11.9%), 24 (22%), 31 (28.4%), 2 (1.8%), 9 (8.3%) and 2 (1.8%) cases for MNF116, 34βE12, CK7, CK14, AE1/3, Cam5.2, respectively. CD34 was expressed in 79 (72.5%) cases. There was no stromal staining for p63. Stromal MNF116, 34βE12 and Cam5.2 reactivity was significantly associated with phyllodes tumour grade (p=0.027, p=0.034, p=0.009 respectively), while MNF116 stromal staining was observed in tumours with increasing cellularity (p=0.036), necrosis (p=0.015) and cystic change (p=0.048). Contrary to common understanding, these findings confirm that stromal cells in phyllodes tumours can sometimes express keratins, albeit focal and in a patchy distribution. In comparison, fibromatosis and dermatofibrosarcoma were uniformly negative for the same keratin panel, while spindle cell components of eight metaplastic carcinomas expressed at least two or more keratins in a wider distribution of up to 90% of positively stained spindle cells. All eight spindle cell sarcomas were negative for keratins.
The use of keratins as an adjunctive immunohistochemical diagnostic tool in the differential work-up of spindle cell tumours of the breast has to be interpreted with caution especially on limited core biopsy material.
Journal of clinical pathology 01/2012; 65(4):339-47. · 2.43 Impact Factor
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ABSTRACT: To define a predictive model for clinical behaviour of breast phyllodes tumours (PT) using histological parameters and surgical margin status.
Cases of breast PT diagnosed in the Department of Pathology Singapore General Hospital between January 1992 and December 2010 were stratified into benign, borderline and malignant grades based on a combination of histological parameters (stromal atypia, hypercellularity, mitoses, overgrowth and nature of tumour borders). Surgical margin status was assessed. Clinical follow-up and biostatistical modelling were accomplished.
Of 605 PT, 440 (72.7%) were benign, 111 (18.4%) borderline and 54 (8.9%) malignant. Recurrences, which were predominantly local, were documented in 80 (13.2%) women. Deaths from PT occurred in 12 (2%) women. Multivariate analysis revealed stromal atypia, overgrowth and surgical margins to be independently predictive of clinical behaviour, with mitoses achieving near significance. Stromal hypercellularity and tumour borders were not independently useful. A nomogram developed based on atypia, mitoses, overgrowth and surgical margins (AMOS criteria) could predict recurrence-free survival at 1, 3, 5 and 10 years. This nomogram was superior to a total histological score derived from adding values assigned to each of five histological parameters.
A predictive nomogram based on three histological criteria and surgical margin status can be used to calculate recurrence-free survival of an individual woman diagnosed with PT. This can be applied for patient counselling and clinical management.
Journal of clinical pathology 11/2011; 65(1):69-76. · 2.43 Impact Factor
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ABSTRACT: To document and clarify the nature of intranuclear inclusions of luminal epithelium in benign proliferative breast lesions.
Five benign breast lesions were selected which showed intranuclear inclusions within epithelial cells on light microscopy. Following confirmation of their luminal epithelial (non-myoepithelial) localisation by immunohistochemistry, ultrastructural examination was performed with the following observations: (1) presence of deep nuclear indentations occasionally verging on nuclear inclusions; (2) inclusions with features of helioid bodies; and (3) a morphological spectrum of helioid bodies and their focal coexistence.
Intranuclear inclusions of breast epithelium are likely of cytoplasmic origin. Helioid bodies may be formed by a stepwise process, the nature of which needs further study.
Journal of clinical pathology 06/2011; 64(9):776-80. · 2.43 Impact Factor
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ABSTRACT: Breast phyllodes tumors are rare neoplasms which present challenges for histological classification. Microscopic features are not always predictive of clinical behavior, and scarce data exist on the prognostic role of biological markers. Our study evaluated a series of 145 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital between 2006 and 2009, incorporating 91 (62.8%) benign, 40 (27.6%) borderline, and 14 (9.7%) malignant phyllodes tumors. Antibodies to keratin 15 (KRT15), transcobalamin I (TCN1), and homeobox gene Hox-B13 (HOXB13) were applied to sections cut from tissue microarray blocks. KRT15 and TCN1 positivity was defined when there was reactivity of 1% or more stromal cells, while HOXB13 positivity was defined using a H-score of 100 and above. Positive immunohistochemical expression for KRT15, TCN1, and HOXB13 was seen in 21 (14.5%), 96 (66.2%), and 66 (45.5%) of tumors, respectively. Stromal expression of KRT15, TCN1, and HOXB13 was significantly correlated with tumor grade (P < 0.001, P < 0.001, P = 0.012), stromal hypercellularity (P = 0.005, P < 0.001, P = 0.023), mitotic activity (P < 0.001), and microscopic borders (P = 0.006, P < 0.001, P = 0.011). Co-expression of TCN1 and HOXB13 was seen in 21 of 91 (23.1%) benign, 18 of 40 (45.0%) borderline, and 11 of 14 (78.6%) malignant tumors, suggesting that the dual-marker panels of TCN1 and HOXB13 might be helpful in classifying borderline and malignant tumors. Although expression of TCN1 alone was present in all malignant and 34 of 40 (85.0%) borderline tumors, a combined panel with HOXB13 excluded some benign cases and was a better discriminant for a significant proportion of borderline and malignant tumors.
Breast Cancer Research and Treatment 05/2011; 132(1):143-51. · 4.43 Impact Factor
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ABSTRACT: Triple negative breast cancer is associated with poorer prognosis and unresponsiveness to endocrine and anti-HER2 directed agents. Despite emerging data supporting the use of polyADP-ribose polymerase (PARP) inhibitors, complete and durable responses are rare and exploration of additional targeted therapies is needed. Epidermal growth factor receptor (EGFR) is expressed in triple negative breast cancer and several clinical trials are testing the role of anti-EGFR directed therapy. However, the rate of EGFR mutations is poorly defined. We, therefore, sought to characterize EGFR mutations in triple negative breast cancers.
Seventy samples were randomly chosen from a cohort of 653 triple negative breast tumours for EGFR mutation analysis. These samples were immunostained for EGFR protein expression and consisted of negatively stained and positively stained cases. DNA was extracted from paraffin blocks and polymerase chain reaction was performed to amplify exon regions 18 to 21 of the EGFR gene. Direct sequencing of the purified PCR products was performed.
EGFR mutations were found in 8 of 70 samples (11.4%). Mutations were predominantly exon 19 deletions (4 of 70 samples, 5.7%), which clustered in the region spanning codons 746 to 759 within the kinase domain of EGFR. Two types of exon 19 deletions were seen: a 15 nucleotide deletion (del E746-A750) (2 of 70 samples) and a 24 nucleotide deletion (del S752 - I759) (2 of 70 samples). Other exon 19 mutations observed were the inversion of the complementary strand (1 of 70 samples). Exon 21 mutations included missense substitution, L858R (1 of 70 samples) and T847I (2 of 70 samples). Mutations observed were independent of EGFR protein expression determined by immunohistochemical staining.
This study is among the first to document the presence and estimate the prevalence of EGFR mutations in triple negative breast cancer. These findings have potential implications for the design of clinical trials involving anti-EGFR directed therapy which currently do not select for patients based on presence of activating EGFR mutations, which may hence be underpowered to detect significant benefit in unselected populations. More complete sampling of EGFR mutation status in triple negative breast cancer is needed to determine the true mutation rate.
Breast cancer research: BCR 04/2011; 13(2):R35. · 5.24 Impact Factor
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ABSTRACT: Histiocytoid breast carcinoma is an uncommon entity that is mostly regarded as a variant of lobular carcinoma. Its occurrence with apocrine lobular carcinoma in situ and consistent expression of gross cystic disease fluid protein 15 suggest apocrine differentiation. Its recognition is often challenging, particularly when histiocytoid tumour cells occur in a metastatic site before the primary diagnosis of breast carcinoma, or in limited core biopsy or cytology material. In the breast, its bland histological appearances can lead to a benign diagnosis. Clues to the correct conclusion include finding tumour cells with more cytological atypia, the presence of cytoplasmic vacuoles and secretions, coexistence with more traditional invasive lobular carcinoma patterns and/or lobular neoplasia, and the use of immuohistochemistry to confirm their epithelial nature. Close clinicoradiological correlation and awareness of histological mimics are needed to achieve an accurate diagnosis of this enigmatic condition that should be appropriately subsumed within the invasive lobular histological subtype.
Journal of clinical pathology 03/2011; 64(8):654-9. · 2.43 Impact Factor
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ABSTRACT: To determine the expression pattern and prognostic value of heparan sulfate in gastric cancer.
The 10E4 antiheparan sulfate monoclonal antibody was used to examine the expression pattern of heparan sulfate in tissue microarrays consisting of 162 cases of gastric carcinoma by immunohistochemistry. The immunoreactivities of both epithelial and stromal components of the specimens were examined and analysed statistically for significant associations with clinicopathological parameters, including histological grade of the tumour, extent of cancer infiltration and presence of lymph-node metastases, lymphovascular invasion, perineural invasion, perforation of gastric wall and stromal reaction. The potential use of heparan sulfate as a predictive factor for patient survival was also evaluated.
Reduced expression of heparan sulfate in the epithelial component was associated with higher histological grades of gastric cancer as well as the presence of more extensive tumour infiltration. Furthermore, this decrease in heparan sulfate expression was found to be predictive of reduced patient survival after tumour recurrence.
The data suggest that heparan sulfate may play an important role in regulating the biology of gastric cancer, and that it may be a useful prognostic marker of this tumour.
Journal of clinical pathology 02/2011; 64(2):153-8. · 2.43 Impact Factor
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ABSTRACT: Immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) are the only tests currently approved by the US Food and Drug Administration for classifying which patients will benefit from trastuzumab therapy. The accuracy of these two testing methods can be adversely affected by a variety of pre-analytical, analytical and post-analytical factors. According to the latest published recommendations of the panel of the Joint Committee of the American Society of Clinical Oncology and College of American Pathologists for HER2/neu testing, laboratories performing IHC and FISH for HER2/neu status in breast cancer are now required to have a high concordance of at least 95% between IHC and FISH, significantly higher than that in the published literature.
To perform a retrospective analysis of the concordance of IHC and FISH analysis for HER2/neu at Singapore General Hospital and review potential causes of disparity between these two methods.
A retrospective review of a total of 106 invasive ductal carcinomas evaluated for HER2/neu at the Department of Pathology, Singapore General Hospital between 2007 and 2008 were included in the study. The initial HER2/neu immunostained slides were reviewed independently without knowledge of FISH results, and concordance between IHC and FISH was determined.
Concordance between IHC and FISH assay was excellent and within the published range (104/106=98.1%). The discordant cases represent a well-recognised subset of genetic heterogeneity in HER2/neu, which is known to contribute to positive IHC and negative FISH tests.
Journal of clinical pathology 02/2011; 64(2):120-4. · 2.43 Impact Factor
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ABSTRACT: Calreticulin is a chaperone protein located in the lumen of the endoplasmic reticulum. The association of calreticulin with pathological conditions such as autoimmune disorders and certain types of cancer have been reported. However, little is known about its role in the pathogenesis of breast cancer. The aim of this study was to determine the expression of calreticulin in vitro and correlate its expression levels in breast cancer tissue samples with clinicopathological parameters. Calreticulin expression was evaluated in MCF-7 and MDA-MB-231 breast cancer cells by real-time RT-PCR, Western blot, immunohistochemistry, and immunofluorescence staining. Patient tissue microarrays were constructed from 228 breast cancer specimens for immunohistochemical analysis. The in vitro study showed a higher calreticulin expression in more aggressive MDA-MB-231 cells as compared with MCF-7 cells at both mRNA and protein levels. In all, 227 out of 228 breast cancer samples exhibited calreticulin staining in at least 5% of the cancer cells. Calreticulin immunostaining was observed to be localized to the cytoplasm of the cancer cells. Regression analysis of calreticulin immunostaining in the tissue microarrays revealed that its expression was positively correlated to logarithm of (log) tumor size (P=0.046) and development of distant metastasis (P=0.017). Multivariate analysis confirmed calreticulin expression as an independent predictor of log tumor size and occurrence of distant metastasis. The data suggest that calreticulin expression is associated with more advanced tumors and is a potential prognostic biomarker.
Modern Pathology 12/2010; 23(12):1559-66. · 4.79 Impact Factor
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ABSTRACT: Phyllodes tumors of the breast are rare fibroepithelial neoplasms with a potential for recurrence. Current histological classification is not always predictive of clinical behavior. The aim of this study was to identify genetic changes associated with the development of borderline and malignant phyllodes tumors in an Asian population, and to assess if genetic data supported the categorization of these tumors into the existing three grades of benign, borderline, and malignant. Expression profiling of 21 phyllodes tumors (6 benign, 10 borderline, 5 malignant) was performed using Affymetrix U133Plus 2.0 GeneChips(®). Gene expression among benign, borderline, and malignant tumors was compared and a 29 gene list was able to classify them according to their histologic grade. Among these 29 genes are those responsible for matrix formation, cell adhesion, epidermis formation, and cell proliferation. Comparative genomic microarray analysis showed that the most common chromosomal alteration associated with borderline and malignant tumors was 1q gain, and an increasing number of chromosomal changes was noted with increasing histological grade. Upregulation of HOXB13 was seen in malignant relative to borderline phyllodes tumors and further investigated by immunohistochemistry in a corresponding set of formalin-fixed, paraffin-embedded tumors. HOXB13 protein overexpression was found to be correlated with stromal hypercellularity and atypia (P = 0.03, P = 0.039, respectively) and may be implicated in the development of malignant phyllodes tumors.
Breast Cancer Research and Treatment 10/2010; 129(2):319-29. · 4.43 Impact Factor
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ABSTRACT: The Y-box-binding protein 1 (YB-1), a member of the cold-shock domain RNA-and DNA-binding protein family, has pleiotropic functions such as regulation of the cell cycle. The aim of this study was to evaluate if YB-1 is a proliferative marker in breast cancer and elucidate potential downstream targets involved in YB-1-mediated cell cycle regulation using RNA interference technology. YB-1 protein expression was evaluated in tissue microarrays of 131 breast invasive ductal carcinomas by immunohistochemistry, while the YB-1 gene expression profile was evaluated in the T-47D, MDA-MB-231, ZR-75-1 and MCF7 breast cancer cell lines. Silencing of the YB-1 gene in T-47D breast cancer cells was performed using siRNA and the effects of down-regulation of YB-1 on cell growth and regulation of the cell cycle were ascertained. A focused panel of 84 genes involved in cell cycle progression was also examined. In tissue microarrays, YB-1 expression was shown to be associated with proliferating cell nuclear antigen (PCNA) immunostaining. siRNA-mediated silencing of the YB-1 gene inhibited cell proliferation and induced G1 phase cell cycle arrest in T-47D breast cancer cells. Knockdown of the YB-1 gene induced up-regulation of two genes which contribute to G1-arrest (RAD9A and CDKN3 genes) and down-regulation of ten genes associated with positive regulation of the cell cycle (SKP2, SUMO1, ANAPC4, CCNB1, CKS2, MNAT1, CDC20, RBBP8, KPNA2 and CCNC genes). The data obtained from the tissue microarrays and cell lines provide evidence that YB-1 is a reliable marker of cell proliferation and possibly a potential molecular target in breast cancer therapy.
International Journal of Oncology 08/2010; 37(2):483-92. · 2.40 Impact Factor
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ABSTRACT: To establish histological and biological parameters that can predict phyllodes tumours on core biopsy specimens of indeterminate fibroepithelial neoplasms.
Core biopsy specimens of fibroepithelial lesions diagnosed at the Department of Pathology, Singapore General Hospital from 2002 to 2007 were reviewed. Cases in which phyllodes tumour was favoured, or could not be ruled out, were evaluated for stromal cellularity/distribution, nuclear atypia and mitoses, stromal overgrowth, epithelial fronding, epithelial hyperplasia, configuration of lesional edge, presence of pseudoangiomatous stromal hyperplasia and of adipose tissue. Antibodies to Ki67, topoisomerase IIalpha, CD34, CD117 and Bcl-2 were applied to sections subjected to immunohistochemistry using the streptavidin-biotin method. Findings were correlated with subsequent excisions. Of 261 core biopsy specimens of fibroepithelial lesions, 98 (37%) comprised cases in which phyllodes tumour could not be excluded and 57 (58%) had subsequent open surgical excisions. Marked stromal hypercellularity (5/5; 100%) and nuclear atypia (1/1; 100%), stromal overgrowth (17/17; 100%), mitoses > or =2/10 high-power fields (18/18; 100%) and ill-defined lesional borders (16/16 phyllodes tumours; 100%) were features in core biopsy specimens that exclusively predicted phyllodes tumour on excision. Moderate stromal hypercellularity (20/27 phyllodes tumours; 74%), stromal overgrowth, moderate nuclear atypia (14/16 phyllodes tumours; 87%), pseudoangiomatous stromal hyperplasia (19/23 phyllodes tumours; 83%) significantly correlated with their subsequent excisions. Immunohistochemical markers Ki67 > or =5% and topoisomerase IIalpha> or =5%, and reduced or patchy CD34 on core biopsy specimens correlated significantly with a diagnosis of phyllodes.
Stromal hypercellularity, combined with key histological features and immunohistochemical markers Ki67, topoisomerase IIalpha and CD34, reinforced by clinical findings, can predict phyllodes tumours on core biopsy specimens.
Histopathology 08/2010; 57(2):220-32. · 3.08 Impact Factor
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ABSTRACT: We earlier evaluated the relationship of 653 triple negative breast cancers (TNBC) with basal immunophenotypic expression by using antibodies to basal cytokeratins (CK5/6, CK14, CK17, 34betaE12), p63, smooth muscle actin (SMA), epidermal growth factor receptor, and CD117, and found that a triple panel of CK14, 34betaE12 and epidermal growth factor receptor determined 84% of our cases to be basal-like. Women with basal-like TNBC tended to be younger (P=0.04), have histologically higher-grade tumors (P=0.047), with positive nodal status (P=0.047), than those whose tumors were nonbasal-like. Using univariate Cox regression analysis, tumor size (P=0.003), histologic grade (P=0.006), and nodal status (P=0.017) were significant factors for disease-free survival (DFS) among TNBC, whereas age (P=0.004), tumor size (P=0.001), histologic grade (P<0.001), nodal status (P=0.011), lymphovascular invasion (P=0.032), and pushing borders (P=0.042) were important for overall survival (OS). On multivariate analysis, age was statistically significant for both DFS and OS (P=0.033, 0.001 respectively), whereas histologic grade was important for OS (P<0.001). Kaplan Meier curves showed CK17 positivity to impact adversely on DFS (P=0.003) and OS (P=0.014), whereas CD117 positive staining was accompanied by diminished OS (P=0.036). SMA expression in TNBC however, revealed a trend for improved DFS (P=0.05). Our findings indicate that basal-like TNBC are associated with adverse clinicopathologic parameters, and that individual biologic markers of CK17, CD117, and SMA have prognostic implications on survival. Possibilities exist for future targeted therapy for this challenging group of breast cancers.
The American journal of surgical pathology 07/2010; 34(7):956-64. · 4.06 Impact Factor
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ABSTRACT: There are limited data that compare the utility of immunohistochemical detection of mammaglobin with Gross Cystic Disease Fluid Protein-15 (GCDFP-15) in locally recurrent and metastatic breast cancers. Forty-three local and 72 distant recurrences of breast cancer, 8 metastatic lesions to the breast from other organs, and 30 metastases from non-breast primaries were immunohistochemically stained with mammaglobin and GCDFP-15 antibodies. Mammaglobin was expressed in 55 (47.8%) and GCDFP-15 detected in 13 (11.3%) locally and distantly recurrent breast cancers. A higher percentage of tumor cells was stained with mammaglobin at greater staining intensity than GCDFP-15, for both metastatic and locally recurrent breast cancers. The difference in staining intensity as well as mean percentage of tumor cells stained for both markers was statistically significant (p < 0.005). Metastases to the breast from other organs and metastatic lesions from non-breast primaries were uniformly negative for both mammaglobin and GCDFP-15. Our study demonstrates that immunohistochemical analysis of mammaglobin is superior to GCDFP-15 in detecting a tumor of breast origin, and can be incorporated into immunohistochemical panels evaluating tumors from unknown primary sites.
Breast (Edinburgh, Scotland) 03/2010; 19(5):355-9. · 2.09 Impact Factor
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ABSTRACT: Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are therapeutically and prognostically important markers in the management of breast carcinoma. They are not always analyzed in distant metastatic and locally recurrent breast cancers. We compared immunohistochemical expression in a series of primary breast carcinomas with their distant metastases (n = 72) and local recurrences (n = 45) and analyzed the impact of any changes on survival. Discordance rates between primary and metastatic and between primary and locally recurrent lesions, respectively, were 18% (13/72) and 13% (6/45) for ER, 42% (30/72) and 33% (15/45) for PR, and 7% (5/72) and 2% (1/45) for c-ERBB2. There was statistically significant discordance between primary and metastatic PR status (P = .017; kappa = 0.201). Among locally recurrent tumors, 15 (33%) of 45 revealed discordance for PR (P = .006; kappa = 0.366). We observed a trend for shorter survival among women with ER- metastatic and locally recurrent tumors regardless of the primary tumor ER status. Our findings suggest a benefit for routine evaluation of ER, PR, and c-ERBB2 status in distant metastatic and locally recurrent breast cancer for therapeutic and prognostic purposes.
American Journal of Clinical Pathology 03/2010; 133(3):416-29. · 2.60 Impact Factor
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Pathology 01/2010; 42(5):498-9. · 2.38 Impact Factor
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ABSTRACT: The increase in early detection of prostate cancer in the Asian population has bolstered second opinion consultations in prostate pathology in this region. In this review, we aimed to identify the spectrum of lesions and queries submitted to a pathologist with uropathology interest at the Singapore General Hospital.
Request forms for second opinion prostate consultations from pathologists and clinicians were retrieved from central laboratory records and a specialist's correspondence files within 2004-2007. Histomorphological queries raised in the referrals, and comparison of original diagnosis and Gleason scoring with the review diagnoses were collated.
Discordant diagnoses (183/323, 57%) were more common than concordant diagnoses (143/326, 44%) between original diagnosis and subspecialist review. The majority of discordances comprised initial undergrading of Gleason scores (132/183, 72%; p < 0.01) especially in needle core biopsies. Among the significantly altered pathological diagnoses, 24 cases (13%; p < 0.01) were changed from benign to malignant (n = 9, 5%; p < 0.01), and malignant to benign (n = 11, 6%; p < 0.01) or high grade prostatic intraepithelial neoplasia (n = 4, 2%; p < 0.01). Benign mimics of malignancy such as atypical adenomatous hyperplasia and atrophy, and small foci of adenocarcinoma, were some examples of morphological pitfalls.
Prostate biopsy review is important because of management and prognostic implications that vary among Gleason scores, and predictive parameters that are detailed in prostate pathology reports.
Pathology 01/2010; 42(1):6-14. · 2.38 Impact Factor
